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      Pesticide Use and Cutaneous Melanoma in Pesticide Applicators in the Agricultural Heath Study

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          Abstract

          Background

          Melanoma rates continue to increase; however, few risk factors other than sun sensitivity and ultraviolet radiation (including sun exposure) have been identified. Although studies of farmers have shown an excess risk of melanoma and other skin cancers, it is unclear how much of this is related to sun exposure compared with other agricultural exposures.

          Methods

          We examined dose–response relationships for 50 agricultural pesticides and cutaneous melanoma incidence in the Agricultural Health Study cohort of licensed pesticide applicators, along with ever use of older pesticides that contain arsenic. Logistic regression was used to examine odds ratios (ORs) and 95% confidence intervals (CIs) associated with pesticide exposure adjusted for age, sex, and other potential confounders.

          Results

          We found significant associations between cutaneous melanoma and maneb/mancozeb (63 exposure days: OR = 2.4; 95% CI, 1.2–4.9; trend p = 0.006), parathion (≥ 56 exposure days: OR = 2.4; 95% CI, 1.3–4.4; trend p = 0.003), and carbaryl (≥ 56 exposure days: OR = 1.7; 95% CI, 1.1–2.5; trend p = 0.013). Other associations with benomyl and ever use of arsenical pesticides were also suggested.

          Conclusions

          Most previous melanoma literature has focused on host factors and sun exposure. Our research shows an association between several pesticides and melanoma, providing support for the hypotheses that agricultural chemicals may be another important source of melanoma risk.

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          Most cited references34

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          The Agricultural Health Study.

          The Agricultural Health Study, a large prospective cohort study has been initiated in North Carolina and Iowa. The objectives of this study are to: 1) identify and quantify cancer risks among men, women, whites, and minorities associated with direct exposure to pesticides and other agricultural agents; 2) evaluate noncancer health risks including neurotoxicity reproductive effects, immunologic effects, nonmalignant respiratory disease, kidney disease, and growth and development among children; 3) evaluate disease risks among spouses and children of farmers that may arise from direct contact with pesticides and agricultural chemicals used in the home lawns and gardens, and from indirect contact, such as spray drift, laundering work clothes, or contaminated food or water; 4) assess current and past occupational and nonoccupational agricultural exposures using periodic interviews and environmental and biologic monitoring; 5) study the relationship between agricultural exposures, biomarkers of exposure, biologic effect, and genetic susceptibility factors relevant to carcinogenesis; and 6) identify and quantify cancer and other disease risks associated with lifestyle factors such as diet, cooking practices, physical activity, smoking and alcohol consumption, and hair dye use. In the first year of a 3-year enrollment period, 26,235 people have been enrolled in the study, including 19,776 registered pesticide applicators and 6,459 spouses of registered farmer applicators. It is estimated that when the total cohort is assembled in 1997 it will include approximately 75,000 adult study subjects. Farmers, the largest group of registered pesticide applicators comprise 77% of the target population enrolled in the study. This experience compares favorably with enrollment rates of previous prospective studies. Images Figure 1. Figure 2. Figure 3. Figure 4.
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            Effects and dose-response relationships of skin cancer and blackfoot disease with arsenic

            In a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than 60 years, a high prevalence of chronic arsenicism has been observed in recent years. The total population of this “endemic” area is approximately 100,000. A general survey of 40,421 inhabitants and follow-up of 1,108 patients with blackfoot disease were made. Blackfoot disease, so-termed locally, is a peripheral vascular disorder resulting in gangrene of the extremities, especially the feet. The overall prevalence rates for skin cancer was 10.6 per 1000, and for blackfoot disease 8.9 per 1000. Generally speaking, the prevalence increased steadily with age in both diseases. The prevalence rates for skin cancer and blackfoot disease increased with the arsenic content of well water, i.e., the higher the arsenic content, the more patients with skin cancer and blackfoot disease. A dose–response relationship between blackfoot disease and the duration of water intake was also noted. Furthermore, the degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and to duration of such intake at the time of onset. The most common cause of death in the patients with skin cancer and blackfoot disease was carcinoma of various sites. The 5-year survival rate after the onset of blackfoot disease was 76.3%; the 10-year survival rate was 63.3% and 15-year survival rate, 52.2%. The 50% survival point was 16 years after onset of the disease. Images FIGURE 1. FIGURE 2.
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              Mechanism of arsenic carcinogenesis: an integrated approach.

              Epidemiological evidence shows an association between inorganic arsenic in drinking water and increased risk of skin, lung and bladder cancers. The lack of animal models has hindered mechanistic studies of arsenic carcinogenesis in the past, but some promising new models for these cancers are now available. The various forms of arsenic to which humans are exposed, either directly or via metabolism of inorganic arsenic to various methylated forms, further complicate the issue of mechanism, since these compounds can have different effects, both genotoxic and non-genotoxic. This review will try to integrate all of these issues, with a strong bias toward effects that are produced by environmentally relevant arsenic concentrations.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                June 2010
                17 February 2010
                : 118
                : 6
                : 812-817
                Affiliations
                [1 ] Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA
                [2 ] Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
                [3 ] Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
                Author notes
                Address correspondence to L.K. Dennis, Department of Epidemiology, College of Public Health, University of Iowa, 200 Hawkins Dr., C21H-GH, Iowa City, IA 52242 USA. Telephone: (319) 384-5010. Fax: (319) 384-5004. E-mail: leslie-dennis@ 123456uiowa.edu

                The authors declare they have no actual or potential competing financial interests.

                Article
                ehp-118-812
                10.1289/ehp.0901518
                2898858
                20164001
                1f8c00fe-90c1-448c-b75c-d0dae5098ead
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 29 September 2009
                : 17 February 2010
                Categories
                Research

                Public health
                melanoma,farmers,arsenic,pesticides
                Public health
                melanoma, farmers, arsenic, pesticides

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